肝細胞癌多段階発癌の画像診断に関する臨床的・基礎的研究

2011 Fiscal Year Annual Research Report

• Project/Area Number: 21591549
• Research Institution: Kanazawa University
• Principal Investigator: 松井 修 金沢大学, 医学系, 教授 (10019961)
• Keywords: 肝細胞癌 / Gd-EOB-DTPA造影MRI / 信号強度 / AFP / PIVKA-II / 悪性度

Research Abstract

【目的】Gd-EOB-DTPA造影MRI肝細胞造影相で等～高信号を呈する肝細胞癌の生物学的特徴を解明するため、腫瘍マーカーAFPおよびPIVKA-IIの産生と組織像とに着目し、低信号肝細胞癌との比較により検討を行った。
【対象・方法】外科的切除または生検で診断された肝細胞癌179結節を対象とし、EOB造影MRI肝細胞造影相で背景肝と比較して低信号を呈する群(n=145)と、等または高信号を呈する群(n=34)とに分類し、以下の項目について比較検討した。
1.MRI撮影前後1ヶ月以内の血中のAFP濃度(ng/ml)とAFP-L3分画(%)、PIVKA-II濃度(mAU/ml)。
2.切除または生検標本の免疫染色によるAFPおよびPIVKA-II発現の半定量的評価(grade O:発現なし,grade 1:弱発現,grade 2:中等度発現,grade 3:強発現)。
3.HE染色による組織像(サイズ、肉眼型、分化度、脈管浸潤、被膜浸潤、肝内転移等)の評価。
【結果】血中腫瘍マーカー濃度は低信号群と比較して高信号群で有意に低く、AFPは1082.3ng/ml vs 12.3 ng/ml(P=0.04)、L3分画は18.3% vs 6.2%(P=0.02)、血中PIVKA-IIは1685mAU/ml vs 205mAU/ml(P=0.02)という結果であった。免疫染色おける発現も低信号群と比較して高信号群で有意に減少しており、AFPの免疫染色gradeは0.91 vs 0.26(P=0.0002)、PIVKA-IIのgradeは1.34 vs 0.67(P=0.02)であった。また切除標本の組織像による検討では、低信号群と比較して高信号群では門脈浸潤の頻度が有意に低かった(31.9% vs 6.3%, P=0.04)。分化度等、他の因子については有意差を認めなかった。
【結論】EOB造影MRI肝細胞造影相で等または高信号を呈する肝細胞癌は、低信号肝細胞癌と比較してAFPおよびPIVKA-IIの産生が抑制されており、また組織学的門脈浸潤の頻度が低かった。これらの結果により、等または高信号肝細胞癌は低信号肝細胞癌と比較して生物学的悪性度が低いという可能性が示唆された。

Research Products

• [Journal Article] Intrahepatic cholangiocarcinomas in cirrhosis arehypervascular in comparison with those in normal livers. 2012 Mar 14 (2012)
  • Author(s): Xu J, Igarashi S, Sasaki M, Matsubara T, Yoneda N, Kozaka K, Ikeda H, Kim J, Yu E, Matsui O, Nakanuma Y
  • Journal Title: Liver Int Volume: (Epub ahead of print)
  • DOI: 10.1111/j.1478-3231.2012.02783.x
  • Peer Reviewed
• [Journal Article] Consensus report of the 4th International Forum for Gadolinium-Ethoxybenzyl-DiethylenetriaminePentaacetic Acid Magnetic Resonance Imaging (2011)
  • Author(s): Lee JM, Zech CJ, Bolondi L, Jonas E, Kim MJ, Matsui O, Merkle EM, Sakamoto M, Choi BI.
  • Journal Title: Korean J Radiol Volume: 12(4) Pages: 403-415
  • Peer Reviewed
• [Journal Article] The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis : correlation with gadoxetic acid enhanced MR imaging (2011)
  • Author(s): Kitao A, Matsui O, Yoneda N, Kozaka K, Shinmura R, Koda W, Kobayashi S, Gabata T, Zen Y, Yamashita T, Kaneko S, Nakanuma Y.
  • Journal Title: Eur Radiol Volume: 21(10) Pages: 2056-2066
  • Peer Reviewed
• [Journal Article] Effect of change in transporter expression on gadolinium-ethoxybenzyl-diethylenetriami nepentaacetic acid-enhanced magnetic resonance imaging during hepatocarcinogenesis in rats (2011)
  • Author(s): Tsuda N, Harada K, Matsui O
  • Journal Title: J Gastroenterol Hepatol Volume: 26(3) Pages: 568-576
  • DOI: DOI:10.1111/j.1440-1746.2010.06494.x
  • Peer Reviewed
• [Journal Article] Signal profile on Gd-EOB-DTPA-enhanced MR imaging in non-alcoholic steatohepatitis and liver cirrhosis induced in rats : correlation with transporter expression (2011)
  • Author(s): Tsuda N, Matsui O
  • Journal Title: Eur Radiol Volume: 21(12) Pages: 2542-2450
  • Peer Reviewed
• [Journal Article] HCC Expert Panel of Japan Society of Hepatology. Management of hepatocellular carcinoma in Japan : Consensus-Based Clinical Practice Guidelinesproposed by the Japan Society of Hepatology (JSH) 2010 updated version (2011)
  • Author(s): Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, Kojiro M, Makuuchi M
  • Journal Title: Dig Dis Volume: 29(3) Pages: 339-364
  • Peer Reviewed
• [Journal Article] Portal blood supply to locally progressed hepatocellularcarcinoma after transcatheter arterial chemoembolization : Observation on CT during arterial portography (2011)
  • Author(s): Miyayama S, Matsui O, Zen Y, Yamashiro M, Hattori Y, Orito N, Matsui K, Tsuji K, Yoshida M, Sudo Y
  • Journal Title: Hepatol Res Volume: 41(9) Pages: 853-866
  • DOI: 10.1111/j.1872-034X.2011.00836.x
  • Peer Reviewed
• [Journal Article] Gadolinium ethoxybenzyl diethylenetriamine pentaacetic Acid-enhanced magnetic resonance imaging findings of borderline lesions at high risk for progression to hypervascular classic hepatocellular carcinoma (2011)
  • Author(s): Kobayashi S, Matsui O, Gabata T, Koda W, Minami T, Ryu Y, Kawai K, Kozaka K
  • Journal Title: J Comput Assist Tomogr Volume: 35(2) Pages: 181-186
  • Peer Reviewed
• [Journal Article] Hepatocelluar nodules in liver cirrhosis : hemodynamic evaluation (angiography-assisted CT) with special reference to multi-stephepatocarcinogenesis (2011)
  • Author(s): Matsui O, Kobayashi s, Sanada J, Kouda W, Ryu Y, Kozaka K, Kitao A, Nakamura K,Gabata T
  • Journal Title: Abdom Imaging Volume: 36(3) Pages: 264-272
  • Peer Reviewed
• [Journal Article] Effectiveness of temporal and dynamic subtraction images of the liver for detection of small HCC on abdominal CT images : comparison of 3D nonlinear image-warping and 3D global-matching techniques (2011)
  • Author(s): Okumura E, Sanada S, Suzuki M, Takemura A, Matsui O
  • Journal Title: Radiol Phys Technol Volume: 4(2) Pages: 109-120
  • Peer Reviewed
• [Presentation] 教育講演「肝腫瘍」 (2011)
  • Author(s): 松井修
  • Organizer: 第39回日本肝臓学会西部会
  • Place of Presentation: 岡山コンベンションセンター(岡山県)(招待講演)
  • Year and Date: 20111209-20111210
• [Presentation] Diagnostic challenge of very early stage HCC : Evaluation of hepato-carcinogenesis with Gd-EOB-DTPA enhanced MRI : correlation with histopathology and transporter expression (2011)
  • Author(s): 松井修
  • Organizer: The 2^<nd> Asia-Pacific Primary Liver Cancer Expert Meeting
  • Place of Presentation: Hyatt Regency Osaka, Osaka(招待講演)
  • Year and Date: 20110701-20110703
• [Presentation] 肝細胞癌の多段階発癌における肝細胞膜トランスポーターOATP8の発現変化:Gd-EOB-DTPA造影MRIとの対比 (2011)
  • Author(s): 松井修、北尾梓、小坂一斗、有井滋樹
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: ホテルグランパシフィックLE DAIBE、東京
  • Year and Date: 20110602-20110603
• [Presentation] HCC : From diagnosis to treatment (2011)
  • Author(s): 松井修
  • Organizer: ESGAR2011
  • Place of Presentation: Venice Congress Center, Italy(招待講演)
  • Year and Date: 20110521-20110524
• [Presentation] Evaluation of hepatocarcinogenesis with Gd-EOB-DTPA enhanced MRI : Correlation with histopathology and transporter expression (2011)
  • Author(s): 松井修
  • Organizer: ACAE2011
  • Place of Presentation: Beijing, China(招待講演)
  • Year and Date: 20110512-20110515
• [Presentation] 肝細胞癌多段階発癌の血行動態・画像の観察から病理・病態へ:動注CTの導入と多段階発癌・血行動態 (2011)
  • Author(s): 松井修
  • Organizer: 第70回日本医学放射線学会総会
  • Place of Presentation: パシフィコ横浜、神奈川県(招待講演)
  • Year and Date: 20110407-20110410
• [Presentation] Diagnosis and management of HCC-role of primovist-enhanced MRI in Guiding treatment strategy (2011)
  • Author(s): 松井修
  • Organizer: The 5^<th> International Forum for Liver-MRI
  • Place of Presentation: Sheraton Muenchen Arabe llapark Hotel, Germany(招待講演)
  • Year and Date: 2011-09-16
• [Book] 肝細胞癌の早期診断:画像と分子マーカー (2012)
  • Author(s): 有井滋樹、松井修
  • Publisher: アークメディア